title: Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers.
abstract: In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l( - 1). Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α(v)β(3) integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.
authors.affiliation: Department of Chemistry, Institute for Lasers, Photonics and Biophotonics, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Ken-Tye
authors.initials: KT
authors.lastname: Yong
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
authors.forename: Wing-Cheung
authors.initials: WC
authors.lastname: Law
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Liwei
authors.initials: L
authors.lastname: Liu
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Bergey
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
mesh_terms: D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000138:chemical synthesis*; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008297:Male; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D053769:Nanocapsules; D009842:Oligopeptides; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid